Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA hypermutation.
Keratinocyte differentiation induces APOBEC3A, 3B, and mitochondrial DNA hypermutation.
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角质形成细胞分化诱导 APOBEC3A、3B 和线粒体 DNA 超突变
DOI：
10.1038/s41598-018-27930-z
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发表时间：
2018-06-27
影响因子：
4.6
通讯作者：
Muramatsu M
中科院分区：
文献类型：
--
作者：
Wakae K;Nishiyama T;Kondo S;Izuka T;Que L;Chen C;Kase K;Kitamura K;Mohiuddin M;Wang Z;Ahasan MM;Nakamura M;Fujiwara H;Yoshizaki T;Hosomochi K;Tajima A;Nakahara T;Kiyono T;Muramatsu M
线粒体DNA（mtDNA）突变在许多类型的癌症中被发现，并被怀疑参与致癌作用，尽管其机制尚未阐明。在这项研究中，我们报告了连续的C-to-T突变（超突变），一个独特的突变APOBECs诱导，发现在宫颈发育不良和口咽癌的mtDNA。在体外，我们发现，APOBEC 3A（A3 A）和3B（A3 B）的表达，以及mtDNA超突变，诱导宫颈发育不良细胞系W12时，在分化条件下培养。A3 A或A3 B的异位表达足以使mtDNA发生高突变。W12细胞裂解液的分级分离和免疫细胞化学分析表明，A3 A和A3 B可以包含在细胞内。这些结果提示角质形成细胞分化诱导mtDNA超突变，并揭示其分子机制，涉及A3。线粒体DNA超突变在致癌作用中的可能参与也进行了讨论。
Mitochondrial DNA (mtDNA) mutations are found in many types of cancers and suspected to be involved in carcinogenesis, although the mechanism has not been elucidated. In this study, we report that consecutive C-to-T mutations (hypermutations), a unique feature of mutations induced by APOBECs, are found in mtDNA from cervical dysplasia and oropharyngeal cancers.In vitro, we found that APOBEC3A (A3A) and 3B (A3B) expression, as well as mtDNA hypermutation, were induced in a cervical dysplastic cell line W12 when cultured in a differentiating condition. The ectopic expression of A3A or A3B was sufficient to hypermutate mtDNA. Fractionation of W12 cell lysates and immunocytochemical analysis revealed that A3A and A3B could be contained in mitochondrion. These results suggest that mtDNA hypermutation is induced upon keratinocyte differentiation, and shed light on its molecular mechanism, which involves A3s. The possible involvement of mtDNA hypermutations in carcinogenesis is also discussed.
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影响因子：
30.8
作者：
Burns, Michael B.;Temiz, Nuri A.;Harris, Reuben S.
通讯作者：
Harris, Reuben S.
影响因子：
7.7
作者：
Ju YS;Alexandrov LB;Gerstung M;Martincorena I;Nik-Zainal S;Ramakrishna M;Davies HR;Papaemmanuil E;Gundem G;Shlien A;Bolli N;Behjati S;Tarpey PS;Nangalia J;Massie CE;Butler AP;Teague JW;Vassiliou GS;Green AR;Du MQ;Unnikrishnan A;Pimanda JE;Teh BT;Munshi N;Greaves M;Vyas P;El-Naggar AK;Santarius T;Collins VP;Grundy R;Taylor JA;Hayes DN;Malkin D;ICGC Breast Cancer Group;ICGC Chronic Myeloid Disorders Group;ICGC Prostate Cancer Group;Foster CS;Warren AY;Whitaker HC;Brewer D;Eeles R;Cooper C;Neal D;Visakorpi T;Isaacs WB;Bova GS;Flanagan AM;Futreal PA;Lynch AG;Chinnery PF;McDermott U;Stratton MR;Campbell PJ
通讯作者：
Campbell PJ
影响因子：
56.9
作者：
Ishikawa, Kaori;Takenaga, Keizo;Hayashi, Jun-Ichi
通讯作者：
Hayashi, Jun-Ichi
影响因子：
4.8
作者：
Bause, Alexandra S.;Matsui, Mary S.;Haigis, Marcia C.
通讯作者：
Haigis, Marcia C.
影响因子：
6.7
作者：
Kitamura K;Wang Z;Chowdhury S;Simadu M;Koura M;Muramatsu M
通讯作者：
Muramatsu M